A major advance in dermatologic therapy in the past decade is the suc cessful use of cytotoxic agents by topical application in the treatment of early stages of certain cutaneous malignancies. These include solar keratoses (precursors of squamous cell carcinoma), intraepidermal carcinoma (Bow en's disease), superficial basal cell epithelioma, and early stages of the cu taneous lymphoma, mycosis fungoides. Also responsive to these agents are some virus infections of the skin as herpes simplex, and certain types of warts.5-Fluorouracil (5-FU) is probably the most widely used topical anti metabolite in the treatment of cutaneous precancers. It is a pyrimidine antagonist and alters cell function by inhibiting RNA, and, more important, DNA synthesis. Palliative effects have been produced by 5-FU in a number of human cancers including breast, stomach, large intestine, cervix, and ovary. Falkson & Schultz (1) noted disappearance of solar keratoses in pa tients receiving systemic 5-FU for advanced cancers.The first report of the successful use of topical 5-FU in cutaneous malig nancies was that of Klein et al. (2) who described necrosis of cutaneous me tastases from adenocarcinoma of the colon in two patients following the application of 20 percent 5-FU in a. hydrophilic base. In a subsequent com munication, Klein and co-workers (3) reported the involution of a lesion of keratoacanthoma with a 20 percent 5-FU ointment without damaging the surrounding skin. Injection of a 5 percent solution of 5-FU at the base of other keratoacanthomas also caused destruction of the tumors.In 1963, Dillaha and collaborators (4) reported excellent results in the treatment of extensive actinic keratoses on the face and neck with 20 percent 5-FU in hydrophilic ointment. Eighteen patients were treated with this preparation twice daily. In two to three days an inflammatory reaction was noted at the site of the keratoses without much change in the surrounding skin. The reaction reached its height in about two weeks at which time the medication was stopped. Healing of the lesions occurred in about two more 1 This study on Topical Antimetabolites was supported by a grant from the Hart ford Foundation. 59 Annu. Rev. Med. 1970.21:59-66. Downloaded from www.annualreviews.org Access provided by University of California -San Diego on 02/03/15. For personal use only. Quick links to online content Further ANNUAL REVIEWS